Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Clinical Trial
. 2025 May;31(6):706-718.
doi: 10.1177/13524585251330085. Epub 2025 Apr 18.

Safety and tolerability of conversion to siponimod from other disease-modifying therapies in patients with advancing forms of relapsing MS: Results from the EXCHANGE study

Robert J Fox  1 , Stanley Cohan  2 , Yang Mao-Draayer  3 , Bianca Weinstock-Guttman  4 , Linda-Ali Cruz  5 , Sophie Arnould  6 , Gina Mavrikis Cox  5 , Amit Bar-Or  7
Affiliations
Clinical Trial

Safety and tolerability of conversion to siponimod from other disease-modifying therapies in patients with advancing forms of relapsing MS: Results from the EXCHANGE study

Robert J Fox et al. Mult Scler. 2025 May.

Abstract

Background: Siponimod, a sphingosine-1-phosphate (S1P) receptor modulator, reduces relapses and delays disability progression in patients with active progressive multiple sclerosis (MS).

Objective: EXCHANGE assessed the safety/tolerability of siponimod in patients with advancing relapsing MS (RMS) converting from other disease-modifying therapies (DMTs).

Methods: This 6-month, open-label, multicenter, single-arm, phase 3b study (NCT03623243) enrolled 185 patients with advancing RMS previously treated with other DMTs for ⩾3 months. Patients were converted to siponimod via a 6-day dose-titration regimen, or converted immediately, depending on prior DMT use.

Results: Treatment-related adverse events (AEs) were reported by 31.9% (59/185) of patients, with headache (8.1%, n = 15), dizziness (3.8%, n = 7), and nausea (3.2%, n = 6) most commonly reported. Overall, an increase in heart rate (HR) 6 hours following the first dose of siponimod was observed (+2.47 bpm [0.66; 4.29]; p = 0.008). Patients switching from fingolimod without dose titration experienced no change in HR. Serious AEs were reported by 4.9% (9/185) of patients, and 8.6% (16/185) of patients discontinued the study treatment due to AEs.

Conclusion: Conversion to siponimod from other DMTs was found to be generally well tolerated. Patients switching from other S1P-receptor modulators may be able to immediately transition to the siponimod maintenance dose without effects on HR.

Clinical trial registration: ClinicalTrials.gov: NCT03623243 (https://clinicaltrials.gov/study/NCT03623243).

Keywords: Bradycardia; S1P modulator; multiple sclerosis; safety; secondary progressive multiple sclerosis; siponimod; treatment satisfaction.

PubMed Disclaimer

Conflict of interest statement

Declaration of conflicting interestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: R.J.F. has received personal consulting fees from AB Science, Biogen, Bristol Myers Squibb, Eli Lilly and Company, EMD Serono, Genentech, Genzyme, Greenwich Biosciences, Immunic, iNmune Bio, Janssen, Novartis, Sanofi, Siemens, and TG Therapeutics; has served on advisory committees for AB Science, Biogen, Immunic, Janssen, Novartis, and Sanofi; and has received clinical trial contract and research grant funding from Biogen, Novartis, and Sanofi. S.C. has received speaker fees from Biogen, Bristol Myers Squibb, Novartis, Roche/Genentech, and Sanofi-Genzyme; has served on advisory boards or as a consultant for Biogen, Bristol Myers Squibb, EMD Serono, Novartis, and Sanofi-Genzyme; and has received institutional (the Providence Brain and Spine Institute) research support from AbbVie, Adamas, Biogen, EMD Serono, MedDay, Novartis, Roche/Genentech, Sage Bionetworks, and Sanofi-Genzyme. Y.M-.D. has served as a consultant for and/or received grant support from: Acorda, Bayer, Biogen, Celgene/Bristol Myers Squibb, EMD Serono, Horizon, Janssen, Novartis, Questor, Roche/Genentech, Sanofi-Genzyme, TG Therapeutics, and Teva and has received grants from Chugai, the NIH NIAID Autoimmune Center of Excellence (UM1-AI110557-05, UM1 AI144298-01), Novartis, PCORI, and Sanofi-Genzyme. B.W-.G. has received consulting fees from Biogen, Bristol Myers Squibb, EMD Serono, Immunex, and SANA and has received research support from Biogen, Bristol Myers Squibb, EMD Serono, Genentech, and Novartis. L-.A.C. and G.M.C. are employees and stockholders of Novartis. S.A. is an employee and stockholder of Novartis AG. A.B-.O. has received personal fees for advisory board participation and/or consulting from Abata, Accure, Atara, Biogen, Bristol Myers Squibb/Celgene/Receptos, GlaxoSmithKline, Gossamer, Horizon, Immunic, Janssen/Actelion, Medimmune, Merck/EMD Serono, Novartis, Roche/Genentech, Sangamo, Sanofi-Genzyme, and Viracta; and has received grant support to the University of Pennsylvania from Biogen, Merck/EMD Serono, Novartis, and Roche/Genentech.

Figures

Figure 1.
Figure 1.
Study design of EXCHANGE. aInjectable DMTs: IFNß-1a, IFNß-1b, GA, and pegIFNß-1a. bPatients previously treated with fingolimod were either converted immediately to a maintenance dose of SIPO (2 mg) or underwent dose titration to enhance understanding of the role of titration when converting between S1P receptor modulators. cDefined as cessation of existing DMT and initiation of SIPO within 24 hours, followed by subsequent 5-day dose titration. AV: assessment visit; DMT: disease-modifying therapy; EOS: end of study; GA: glatiramer acetate; IFNß: interferon-beta; pegIFN: peginterferon; S1P: sphingosine-1-phosphate; SIPO: siponimod.
Figure 2.
Figure 2.
EXCHANGE patient flow chart.
Figure 3.
Figure 3.
Mean HR at baseline and 6 hours post first dose by prior MS DMTs. bpm: beats per minute; DMT: disease-modifying therapy; HR: heart rate; IFNß: interferon-beta; n: number of patients with measurement; SD: standard deviation.
Figure 4.
Figure 4.
TSQM-9 scores for the domains of Convenience, Effectiveness, and Global satisfaction at baseline and days 28, 84, and 168. Analysis was based on observed data. No imputation was performed for missing data. n: number of patients with measurement; SD: standard deviation; TSQM-9: abbreviated 9-item Treatment Satisfaction Questionnaire for Medication.
Figure 5.
Figure 5.
(a) PST scores at baseline, day 84, and day 168. (b) Change from baseline for PST score at day 84 and day 168. *p ⩽ 0.05, ***p ⩽ 0.0001. CI: confidence interval; n: number of patients with measurement; PST: Processing Speed Test.
Figure 6.
Figure 6.
(a) NfL concentration (pg/mL) at baseline, day 84, and day 168. (b) Change from baseline in NfL concentration (ng/L) at day 84 and day 168. ***p ⩽ 0.001; ns = not significant. CI: confidence interval; n: number of patients with measurement; NfL: neurofilament light chain; ng/L: nanograms per liter.
See this image and copyright information in PMC

References

    1. Compston A, Coles A. Multiple sclerosis. Lancet 2008; 372(9648): 1502–1517. - PubMed
    1. McGinley MP, Goldschmidt CH, Rae-Grant AD. Diagnosis and treatment of multiple sclerosis: A review. JAMA 2021; 325(8): 765–779. - PubMed
    1. Saccà F, Lanzillo R, Signori A, et al. Determinants of therapy switch in multiple sclerosis treatment-naïve patients: A real-life study. Mult Scler 2019; 25(9): 1263–1272. - PubMed
    1. Novartis Mayzent (siponimod). Prescribing information. Basel, Switzerland: Novartis, 2022.
    1. European Medicines Agency. Mayzent. Summary of product characteristics. Amsterdam, The Netherlands: European Medicines Agency, 2024.

Publication types

MeSH terms

Associated data

LinkOut - more resources